Tumor-associated macrophages (TAMs) have immunosuppressive capacity in mouse models of cancer. Here we show that the genetic deletion of the microRNA (miRNA)-processing enzyme DICER in TAMs broadly programs them to a CD11c+MRC1-/low M1-like immunostimulatory phenotype characterized by activated interferon-? (IFN-?)/STAT1/IRF signaling. M1-like TAM programming fostered the recruitment of cytotoxic T-cells (CTLs), including tumor-antigen-specific CTLs, inhibited tumor growth, and enhanced the efficacy of PD1 checkpoint blockade. Bioinformatics analysis of TAM transcriptomes identified a limited set of miRNAs putatively involved in TAM programming. Re-expression of Let-7 in Dicer-deficient TAMs was sufficient to partly rescue the M2-like (protumoral) TAM phenotype and abate tumor CTL infiltration. Targeted suppression of DICER activity in TAMs may, therefore, stimulate antitumor immunity and enhance the efficacy of cancer immunotherapy. Overall design: To explore the role of DICER in the development, activation and immunological functions of TAMs, we crossed homozygous LysM-Cre (Clausen et al., 1999) with Dicerlox/lox (Harfe et al., 2005) mice to obtain mice with myeloid-cell-specific Dicer1 gene deletion (LysM-Cre;Dicer–/–, referred to as D–/–). These mice were then backcrossed to LysM-Cre to obtain the control LysM-Cre; Dicer+/+ mice (referred to as D+/+). Both LysM-Cre and Dicerlox/lox mutations were always homozygous in our experiment. We then inoculated Lewis lung carcinoma (LLC) cells subcutaneously (s.c.) in D–/– and control D+/+ mice. Once the tumors were established, we isolated by fluorescence-activated cell sorting (FACS) tumor-associated macrophages (F4/80+ cells).
Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity.
Specimen part, Subject
View SamplesGenome-wide analysis of GBM-derived brain tumor stem cells-like (BTSCs) collected at the Freiburg Medical Center and UAB (JX6)
NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1.
Specimen part, Disease, Disease stage
View SamplesExpression data from HEK293 cells expressing a doxcycline-inducible RANBP6 shRNA
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.
No sample metadata fields
View SamplesGain or loss of genes and deregulation of gene expression can result in cumulative and progressive disruptions of normal cellular functions.
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Specimen part
View SamplesGain or loss of genes and deregulation of gene expression can result in cumulative and progressive disruptions of normal cellular functions.
In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Sex, Specimen part
View SamplesMicroarray analysis of murine microglia from different stages of development was performed. Results showed that different phases of microglia development had different group of genes up-regulated for specific functions.
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Specimen part
View SamplesRNAseq was performed on microglia from male and female, SPF or GF mice to elucidate the genetic differences implicated by microbiota and gender. DEGs between the various groups gave some ideas on what different pathways or functions might be affected due to the different factors. Overall design: Microglia from SPF and GF mice from embryonic and adult stages of both gender were sorted for sequencing. DEGs were obtained to observe if any signicant genes were affected. Pathway analysis was performed with the set of DEGs.
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Specimen part, Cell line, Subject
View Samples